(-) 伪酸B的总合成
Barry M Trost1, Jerome Waser, Arndt Meyer
1Department of Chemistry, Stanford University, Stanford, California 94305-5080, USA. bmtrost@stanford.edu
Journal of the American Chemical Society
|November 8, 2007
概括
研究人员首次实现了伪酸B的酶选择合成,这种天然产品具有抗真菌和细胞毒性作用. 这一突破利用了新的循环添加和激进循环化方法来构建复杂的分子.
科学领域:
- 有机化学 有机化学
- 自然产品的合成自然产品的合成
- 药用化学 医学化学
背景情况:
- 伪酸B是一种来自Pseudolarix kaempferi树皮的迪特尔酸.
- 它表现出抗真菌,抗生育和细胞毒性活动,特别是在对抗多药耐药细胞系.
- 复杂的多酸核是一个合成的挑战.
研究的目的:
- 报告第一个伪酸B的选择性合成.
- 开发高效的合成策略来构建自然产品的核心结构.
- 为进一步的生物评估提供B类伪酸的获取.
主要方法:
- 金属催化 [5 + 2] 乙烯基cyclopropane-alkyne 内部分子循环添加,用于聚酸核结构.
- 内部分子氧碳基基循环形成四元中心.
- 用于引入碳氧酸侧链的灾难选择性乙化物添加剂.
主要成果:
- 成功进行了伪酸B (1a) 的酶选择性合成.
- 通过使用关键的C-C键形成反应,高效地构建三环架.
- 建立四元中心和立体选择性安装酸侧链.
结论:
- 开发的合成途径提供了一种可行的方法来获取B型伪酸.
- 使用的方法对于构建复杂的多环自然产品是有效的.
- 这种合成使得可以进一步研究伪酸B的生物活性.
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